tbuckley/cabot-search huggingface dataset:
Micronutrient deficiencies among preschool-aged children and women of reproductive age worldwide: a pooled analysis of individual-level data from population-representative surveys
Authors: Gretchen A Stevens, Ty Beal, Mduduzi N N Mbuya, Hanqi Luo, Lynnette M Neufeld, O Yaw Addo, Seth Adu-Afarwuah, Silvia Alayón, Zulfiqar Bhutta, Kenneth H Brown, Maria Elena Jefferds, Reina Engle-Stone, Wafaie Fawzi, Sonja Y Hess, Robert Johnston, Joanne Katz, Julia Krasevec, Christine M McDonald, Zuguo Mei, Saskia Osendarp, Christopher J Paciorek, Nicolai Petry, Christine M Pfeiffer, Maria J Ramirez-Luzuriaga, Lisa M Rogers, Fabian Rohner, Vani Sethi, Parminder S Suchdev, Masresha Tessema, Salvador Villapando, Frank T Wieringa, Anne M Williams, Meseret Woldeyahannes, Melissa F Young
Journal: The Lancet Global Health (2022)

Micronutrient deficiencies compromise immune systems, hinder child growth and development, and affect human potential worldwide. Yet, to our knowledge, the only existing estimate of the global prevalence of micronutrient deficiencies is from over 30 years ago and is based only on the prevalence of anaemia. We aimed to estimate the global and regional prevalence of deficiency in at least one of three micronutrients among preschool-aged children (aged 6-59 months) and non-pregnant women of reproductive age (aged 15-49 years).
Clonal haematopoiesis of indeterminate potential: associations with heart failure incidence, clinical parameters and biomarkers
Authors: Canxia Shi, Joseph Pierre Aboumsallem, Navin Suthahar, Aniek O. de Graaf, Joop H. Jansen, Isabelle A. van Zeventer, Valentina Bracun, Sanne de Wit, Elles M. Screever, Pieter F. van den Berg, Wouter C. Meijers, Ron T. Gansevoort, Stephan J.L. Bakker, Pim van der Harst, Herman H.W. Silljé, Gerwin Huls, Rudolf A. de Boer
Journal: European Journal of Heart Failure (2022)

We aimed to analyse the association of clonal haematopoiesis of indeterminate potential (CHIP) with incident heart failure (HF) in a European population cohort.From the prospective Prevention of Renal and Vascular End-stage Disease (PREVEND) cohort, we included all 374 participants with incident HF and selected 1:1 age- and sex-matched control subjects. Peripheral blood samples of 705 individuals were successfully analysed by error-corrected next generation sequencing for acquired mutations at a variant allele frequency ≥2% in 27 CHIP driver genes. The median age of the study population was 65 years (interquartile range 58-70) and 35.6% were female. CHIP mutations positively correlated with age, smoking, hypertension and cardiovascular biomarkers including N-terminal pro-B-type natriuretic peptide and mid-regional pro-A-type natriuretic peptide, but the frequency of CHIP was comparable in individuals with incident HF and in control participants (18.4% vs. 17.3%; p = 0.69). In multivariable Cox regression models, CHIP was not significantly associated with incident HF (hazard ratio [HR] 1.24, 95% confidence interval [CI] 0.93-1.65; p = 0.144). This association, however, was modified by age (p for CHIP-age interaction = 0.002). Among people younger than 65 years, CHIP mutations were more frequently detected in the case cohort compared to the control cohort (14.2% vs. 5.8%; p = 0.009), and were significantly associated with new-onset HF (HR 2.07, 95% CI 1.30-3.29; p = 0.002).Clonal haematopoiesis of indeterminate potential correlates with HF risk factors and biomarkers, and is associated with incident HF in subjects <65 years of age.
Long‐term outcomes following catheter ablation versus medical therapy in patients with persistent atrial fibrillation and heart failure with reduced ejection fraction
Authors: Rosita Zakeri, Nikhil Ahluwalia, Alexander Tindale, Fatima Omar, Matthew Packer, Habib Khan, Victoria Baker, Shohreh Honarbakhsh, Mark J. Earley, Simon Sporton, Richard J. Schilling, David Jones, Vias Markides, Ross J. Hunter, Tom Wong
Journal: European Journal of Heart Failure (2022)

Aims The ARC‐HF and CAMTAF trials randomized patients with persistent atrial fibrillation (AF) and heart failure (HF) to early routine catheter ablation (ER‐CA) versus pharmacological rate control (RC). After trial completion, delayed selective catheter ablation (DS‐CA) was performed where clinically indicated in the RC group. We hypothesized that ER‐CA would result in a lower risk of cardiovascular hospitalization and death versus DS‐CA in this population. Methods and results Overall, 102 patients were randomized (age 60 ± 11 years, left ventricular ejection fraction [LVEF] 31 ± 11%): 52 to ER‐CA and 50 to RC. After 12 months, patients undergoing ER‐CA had improved self‐reported symptom scores, lower New York Heart Association class (i.e. better functional capacity), and higher LVEF compared to patients receiving RC alone. During a median follow‐up of 7.8 (interquartile range 3.9–9.9) years, 27 (54%) patients in the RC group underwent DS‐CA and 34 (33.3%) patients died, including 17 (32.7%) randomized to ER‐CA and 17 (34.0%) randomized to RC. Compared with DS‐CA, a strategy of ER‐CA exhibited similar risk of all‐cause mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.44–1.77, p = 0.731) and combined all‐cause mortality or cardiovascular hospitalization (aHR 0.80, 95% CI 0.43–1.47, p = 0.467). However, analyses according to treatment received suggested an association between CA and improved outcomes versus RC (all‐cause mortality: aHR 0.43, 95% CI 0.20–0.91, p = 0.028; all‐cause mortality/cardiovascular hospitalization: aHR 0.48, 95% CI 0.24–0.94, p = 0.031). Conclusions In patients with persistent AF and HF, ER‐CA produces similar long‐term outcomes to a DS‐CA strategy. The association between CA as a treatment received and improved outcomes means there is still a lack of clarity regarding the role of early CA in selected patients. Randomized trials are needed to clarify this question.
The FUS/circEZH2/KLF5/ feedback loop contributes to CXCR4-induced liver metastasis of breast cancer by enhancing epithelial-mesenchymal transition
Authors: Peng Liu, Zehao Wang, Xueqi Ou, Peng Wu, Yue Zhang, Song Wu, Xiangsheng Xiao, Yuehua Li, Feng Ye, Hailin Tang
Journal: Molecular Cancer (2022)

Abstract Background Metastasis of breast cancer have caused the majority of cancer-related death worldwide. The circRNAs are associated with tumorigenesis and metastasis in breast cancer according to recent research. However, the biological mechanism of circRNAs in liver metastatic breast cancer remains ambiguous yet. Methods Microarray analysis of three pairs of primary BC tissues and matched hepatic metastatic specimens identified circEZH2. We used RT-qPCR and FISH assays to confirm circEZH2 existence, characteristics, and expression. Both in vivo and in vitro, circEZH2 played an oncogenic role which promoted metastasis as well. A range of bioinformatic analysis, Western blot, RNA pull-down, RIP, ChIP, and animal experiments were used to define the feedback loop involving FUS, circEZH2, miR-217-5p, KLF5, FUS, CXCR4 as well as epithelial and mesenchymal transition. Results In our research, circEZH2 was proved to be upregulated in liver metastases in BC and predicted the worse prognosis in breast cancer patients. Overexpression of circEZH2 notably accentuated the vitality and invasion of BC cells, whereas knockdown of circEZH2 elicited the literally opposite effects. Besides, overexpressed circEZH2 promoted tumorigenesis and liver metastasis in vivo. Moreover, circEZH2 could adsorb miR-217-5p to upregulate KLF5 thus leading to activate FUS transcription which would facilitate the back-splicing program of circEZH2. Meanwhile, KLF5 could upregulated CXCR4 transcriptionally to accelerate epithelial and mesenchymal transition of breast cancer. Conclusions Consequently, a novel feedback loop FUS/circEZH2/KLF5/CXCR4 was established while circEZH2 could be novel biomarker and potential target for BC patients’ therapy.
2022 KLCA-NCC Korea practice guidelines for the management of hepatocellular carcinoma
Journal: Clinical and Molecular Hepatology (2022)

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the fourth most common cancer among men in South Korea, where the prevalence of chronic hepatitis B infection is high in middle and old age. The current practice guidelines will provide useful and sensible advice for the clinical management of patients with HCC. A total of 49 experts in the fields of hepatology, oncology, surgery, radiology, and radiation oncology from the Korean Liver Cancer Association-National Cancer Center Korea Practice Guideline Revision Committee revised the 2018 Korean guidelines and developed new recommendations that integrate the most up-to-date research findings and expert opinions. These guidelines provide useful information and direction for all clinicians, trainees, and researchers in the diagnosis and treatment of HCC.
Targeting NFE2L2/KEAP1 Mutations in Advanced NSCLC With the TORC1/2 Inhibitor TAK-228
Authors: Paul K. Paik, Pang-Dian Fan, Besnik Qeriqi, Azadeh Namakydoust, Bobby Daly, Linda Ahn, Rachel Kim, Andrew Plodkowski, Ai Ni, Jason Chang, Rachel Fanaroff, Marc Ladanyi, Elisa de Stanchina, Charles M. Rudin
Journal: Journal of Thoracic Oncology (2022)
Cerebrovascular damage in subjective cognitive decline: A systematic review and meta-analysis
Authors: Helda Pitti, Patricia Diaz-Galvan, José Barroso, Atef Badji, Jonas K. Olofsson, Eric Westman, Daniel Ferreira, Nira Cedres
Journal: Ageing Research Reviews (2022)

Subjective cognitive decline (SCD) has been postulated as an early marker of Alzheimer's Disease (AD) but it can also be associated to other non-AD pathologies such as Vascular Dementia (VaD). Nevertheless, there is scarce data about SCD as a potential harbinger of cerebrovascular pathology. Thus, we conducted a systematic review and meta-analysis on the association between SCD and cerebrovascular damage measured by neuroimaging markers.This study was performed following the PRISMA guidelines. The search was conducted in 3 databases (PubMed, Scopus and Web of Science) from origin to December 8th, 2021. Primary studies including cognitively unimpaired adults with SCD and neuroimaging markers of cerebrovascular damage (i.e., white matter signal abnormalities, WMSA) were selected. Qualitative synthesis and meta-analysis of studies with a case-control design was performed.Of 241 articles identified, 21 research articles were selected. Eight case-control studies were included for the meta-analysis. A significant overall effect-size was observed for the mean WMSA burden in SCD relative to controls, where the WMSA burden was higher in SCD.Our findings show the potential usefulness of SCD as a harbinger of cerebrovascular disease in cognitively healthy individuals. Further research is needed in order to elucidate the role of SCD as a preclinical marker of vascular cognitive impairment.
Porphyrin Centered Paclitaxel Tetrameric Prodrug Nanoassemblies as Tumor‐Selective Theranostics for Synergized Breast Cancer Therapy
Authors: Xiaodong Ma, Pengfei Wang, Qiwei Wu, Junnian Zhou, Dongqing Wang, Deependra Yadav, Hongbo Zhang, Yuezhou Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract Although having undergone decades of development, nanoparticulate drug delivery vehicles for efficient cancer therapy remain a challenge, confined by low drug loading, instability, and poor cancer tissue selectivity. A self‐assembled prodrug, the combination of prodrug strategy and the self‐assembly merits, represents a special chemical entity which spontaneously organizes into supramolecular composites with defined architecture, therefore also providing a strategy to develop new medications. Paclitaxel (PTX) is still among the most generally prescribed chemotherapeutics in oncology but is restricted by poor solubility. Although photodynamic therapy, with its noninvasive features and barely developed drug resistance, signifies an alternative tool to suppress life‐threatening cancer, sole use hardly fulfills its potential. To this end, a reduction‐activatable heterotetrameric prodrug with the photosensitizer is synthesized, then formulated into self‐assembled nanoparticles (NPs) for tumor imaging and combined chemo‐ and photodynamic therapy. Coating the NPs with amphiphilic polymer distearylphosphatidylethanolamine‐polyethylene glycol‐arginine‐glycine‐aspartate (DSPE‐PEG‐RGD) offers high stability and enables cancer tissue targeting. The as‐prepared NPs enlighten disease cells and reveal more potent cytotoxicity comparing to PTX and the photosensitizer alone. Furthermore, the NPs selectively accumulates into tumors and synergistically inhibits tumor proliferation with reduced side effects in mice.
Red Light‐Responsive Upconverting Nanoparticles for Quantitative and Controlled Release of a Coumarin‐Based Prodrug
Authors: Anaïs Brion, Juliane Chaud, Jérémie Léonard, Frédéric Bolze, Stefan Chassaing, Benoît Frisch, Béatrice Heurtault, Antoine Kichler, Alexandre Specht
Journal: Advanced Healthcare Materials (2022)

Abstract Photolytic reactions allow the optical control of the liberation of biological effectors by photolabile protecting groups. The development of versatile technologies enabling the use of deep‐red or NIR light excitation still represents a challenging issue, in particular for light‐induced drug release (e.g., light‐induced prodrug activation). Here, light‐sensitive biocompatible lipid nanocapsules able to liberate an antitumoral drug through photolysis are presented. It is demonstrated that original photon upconverting nanoparticles (LNC‐UCs) chemically conjugated to a coumarin‐based photocleavable linker can quantitatively and efficiently release a drug by upconversion luminescence‐assisted photolysis using a deep‐red excitation wavelength. In addition, it is also able to demonstrate that such nanoparticles are stable in the dark, without any drug leakage in the absence of light. These findings open new avenues to specifically liberate diverse drugs using deep‐red or NIR excitations for future therapeutic applications in nanomedicine.
Recurrent facial paralysis and weakness
Authors: Vikram Ajit Rajan Thirupathirajan, Thirupathirajan Thinakararajan
Journal: BMJ (2022)

A woman in her 50s presented with a history of at least five paroxysmal episodes of facial paralysis and weakness over 25 years. She first experienced symptoms at age 26, which were bilateral and more severe on the right. No other physical findings were documented during the initial presentation. The severity of symptoms increased with each episode along with complete facial paralysis and were not always followed by full recovery, with intervals between episodes lasting more than eight weeks. About 48 hours before onset of facial paralysis and weakness, the patient usually experienced pain behind the left ear and on the lateral part of the neck. She did not report any skin lesions, fissured tongue, or swelling of the lips or tongue. Box 1 summarises the neurological findings of the most recent presentation. Box 1 ### Findings from neurological examination #### Cranial nerves of head and neck I-VI (olfactory, optic, oculomotor, trochlear, trigeminal, abducens): intact VII (facial): eyelid closure complete, difficulty raising eyebrows on the right side, little movement of lower face on the right side VIII-XII (vestibulocochlear, glossopharyngeal, vagus, accessory, hypoglossal): intact #### Upper limb Normal tone and 5/5 power in all muscle groups Normal reflexes Sensation normal #### Lower limb Normal tone and 5/5 power in all muscle … RETURN TO TEXT
Reducing the health impacts of ambient air pollution
Authors: C Sorensen, E Lehmann, C Holder, J Hu, A Krishnan, T Münzel, Rice MB, Salas RN
Journal: BMJ (2022)

With passive avoidance (PA), Morris water maze (WM) and eight-arm radial maze tasks, we evaluated the memory-enhancing action of FK960 [N-(4-acetyl-1-piperazinyl)-p-fluorobenzamide monohydrate], a compound which we have found through rational drug screening based on our hypothesis that penile erection is a valid predictor of central cholinergic activation. Memory performance in the tasks was impaired in aged (24- to 26-months-old) rats as well as in rats with nucleus basalis magnocellularis lesions. Scopolamine (1 mg/kg i.p.) treatment induced memory impairment in PA and WM; treatment with cysteamine (200 mg/kg s.c.) induced memory impairment in PA but not in WM, whereas fimbria fornix lesioning affected the rats in the opposite manner. FK960 (0.1-10 mg/kg i.p.) ameliorated all the memory impairments except those induced by cysteamine or fimbria fornix lesion, and the dose-response curves were bell shaped with maximal response at 1 to 3.2 mg/kg. The effects of FK960 on the scopolamine-induced memory impairment in the PA and/or WM were abolished by cysteamine (200 mg/kg s.c.), dl-p-chlorophenylalanine methyl ester hydrochloride (150 mg/kg i.p. for 3 days) or raphe lesioning, but not by neonatal 6-hydroxydopamine (35 micrograms/head) treatment. Neurochemical analysis revealed that cysteamine and raphe lesions reduced brain somatostatin and serotonin contents, respectively. The treatment with FK960 (0.32-320 mg/kg p.o.) dose-dependently increased both serotonin and 5-hydroxyindoleacetic acid levels in the brain areas examined and significantly increased hippocampal somatostatin contents at the smaller doses. From these results, we conclude that FK960 ameliorates cognitive dysfunction through an activation of the somatostatinergic-serotonergic link.
It’s time to widen the capture of gestational diabetes in the UK
Authors: Amaju E Ikomi
Journal: BMJ (2022)

<h3>Abstract</h3> Infected wounds pose a major mortality risk in animals. Injuries are common in the ant <i>Megaponera analis</i> which raids pugnacious prey. Here we show that <i>M. analis</i> can determine when wounds are infected and treat them specifically. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds, workers reduce the mortality of infected individuals by 90%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that the targeted use of antimicrobials to treat infected wounds, previously thought to be a uniquely human behavior, has evolved in insect societies as well. <h3>One-Sentence Summary</h3> Ants use antimicrobial compounds and proteins to successfully treat the infected wounds of nestmates.
Inhibition of Pro‐Survival Autophagy Induced by Rare‐Earth Nanocomposites for Promoting Photothermal Therapy of Visualized Tumors
Authors: Shanshan Peng, Lizhen Wang, Lin Liu, Liang Song, Junpeng Shi, Hanrun Zheng, Jixuan Xu, Rui Rong, Yun Zhang
Journal: Advanced Healthcare Materials (2022)

Manipulation of autophagic processes has emerged as a promising strategy for synergizing nanoagent-mediated photothermal therapy (PTT). Most of the current studies focus on improving PTT efficacy by inhibiting pro-survival autophagy induced by the heat generated from the photothermal process. However, autophagy induced by the nanoagents is usually ignored, which may weaken the effect of autophagy-mediated efficacy improvement in PTT if induced autophagy is pro-death. Therefore, this work aims at developing a nanoagent that is able to induce heat-synergetic pro-survival autophagy to optimize the efficacy of PTT. An approach is developed to coat carbon layer, polyethylenimine (PEI), and folic acid (FA) on NaYF4 :Er,Yb,Nd@NaNdF4 (DCNPs@C@PEI@FA, DCPF) nanoparticles successively, giving access to the nanoagent to induce pro-survival autophagy. The synthetic imaging-guided photothermal nanoagent displays outstanding targeting ability and biocompatibility based on the surface modification of PEI and FA. By using an autophagy inhibitor chloroquine, a conspicuously synergistic effect on DCPF-mediated PTT in vitro and in vivo tumor models (HeLa) is achieved. A promising strategy is presented here to enhance the efficacy of imaging-guided PTT by modulating the autophagy induced by the nanoagent.
SCLC: Epidemiology, Risk Factors, Genetic Susceptibility, Molecular Pathology, Screening, and Early Detection
Authors: Qian Wang, Zeynep H. Gümüş, Cristina Colarossi, Lorenzo Memeo, Xintong Wang, Chung Yin Kong, Paolo Boffetta
Journal: Journal of Thoracic Oncology (2022)
Join the fight against fossil fuels
Authors: Rhiannon Osborne
Journal: BMJ (2022)

<h3>Abstract</h3> <h3>Background</h3> Reports of waning vaccine-induced immunity against COVID-19 have begun to surface. With that, the comparable long-term protection conferred by previous infection with SARS-CoV-2 remains unclear. <h3>Methods</h3> We conducted a retrospective observational study comparing three groups: (1)SARS-CoV-2-naïve individuals who received a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, (2)previously infected individuals who have not been vaccinated, and (3)previously infected <i>and</i> single dose vaccinated individuals. Three multivariate logistic regression models were applied. In all models we evaluated four outcomes: SARS-CoV-2 infection, symptomatic disease, COVID-19-related hospitalization and death. The follow-up period of June 1 to August 14, 2021, when the Delta variant was dominant in Israel. <h3>Results</h3> SARS-CoV-2-naïve vaccinees had a 13.06-fold (95% CI, 8.08 to 21.11) increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant (<i>P</i>&lt;0.001) for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold (95% CI, 4.85 to 7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI, 5.51 to 9.21) increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected. <h3>Conclusions</h3> This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalization caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity. Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.
Food Processing and Risk of Crohn’s Disease and Ulcerative Colitis: A European Prospective Cohort Study
Authors: Antoine Meyer, Catherine Dong, Corinne Casagrande, Simon S.M. Chan, Inge Huybrechts, Geneviève Nicolas, Fernanda Rauber, Renata Bertazzi Levy, Christopher Millett, Bas Oldenburg, Elisabete Weiderpass, Alicia K. Heath, Tammy Y.N. Tong, Anne Tjønneland, Cecilie Kyrø, Rudolf Kaaks, Verena A. Katzke, Manuela M. Bergman, Domenico Palli, Giovanna Masala, Rosario Tumino, Carlotta Sacerdote, Sandra M. Colorado-Yohar, Maria-Jose Sánchez, Olof Grip, Stefan Lindgren, Robert Luben, Marc J. Gunter, Yahya Mahamat-Saleh, Marie-Christine Boutron-Ruault, Franck Carbonnel
Journal: Clinical Gastroenterology and Hepatology (2022)